ABSTRACT The randomized controlled trial proposed in this grant application addresses the problem of disproportionately high rates of drug use among sexual-minority adolescents in the United States. Sexual- minority adolescents are youth who self-identify as gay, lesbian, bisexual, or unsure of their sexual orientation. In this application, our sample of sexual-minority youth will also include youth who identify as transgender or unsure of their gender identity. We propose to develop and test a tailored, web-based program to prevent drug use and delay drug use initiation among sexual-minority youth. To date, no such program exists. Study participants will be 15- to 17-year-old youth recruited from Facebook. As the largest and most popular social networking site in the United States, Facebook has approximately 3.8 million registered U.S. users, aged 15 to 17 years. With national data indicating that approximately 7.5% of youth identify as a sexual- minority group member, Facebook provides unparalleled access to this difficult to reach population. The 10-session intervention will be delivered online. The sessions will be housed on a customizable homepage with features youth seek: feeds to current events, entertainment and sports news, fitness and fashion tips, links to popular gaming and social-networking sites, and health-related resources. To address the risk factors for drug use that are salient for all youth?namely managing peer and social influences?session content will provide youth with opportunities to acquire, try out, receive feedback on, and master cognitive-behavioral skills related to: goal setting, problem solving, drug refusal, assertiveness, and normative beliefs. Unlike extant programs, these sessions will be tailored at the surface (e.g., characters, elements of design, lexicon) and structural levels (e.g., scenarios, role-plays) to reflect the everyday realities of sexual-minority youth. To address sexual-minority youths? specific risk factors for drug use?namely the stress associated with internalized homophobia, harassment from peers, and managing family rejection?additional session content will focus on: enhancing self-worth, coping strategies, building social supports, and managing negative moods. The randomized controlled trial will include 890 sexual-minority youth from the United States. All youth will complete pretest measures online. Intervention-arm youth will then interact with the 10-session program; youth in the control arm will have access to an attention-placebo website. All youth will then complete posttest measures and 1-, 2-, and 3-year follow-up measures. Across posttest and annual follow-up measurement occasions, data analyses will examine rates of 30-day drug use and drug use initiation between study arms. We will also examine intervention effects on mediator variables associated with drug use and assess the extent to which changes in mediator variables explain differences in drug use between arms.